Data from: Glucocorticoid induces incoordination between glutamatergic and GABAergic neurons in the amygdala

Background: Stressful life leads to mood disorders. Chronic mild stress is presumably major etiology for depression, and acute severe stress leads to anxiety. These stressful situations may impair hypothalamus-pituitary-adrenal axis and in turn induce synapse dysfunction. However, it remains elusive how the stress hormones mess up subcellular compartments and interactions between excitatory and inhibitory neurons, which we have investigated in mouse amygdala, a structure related to emotional states. Methods and Results: Dexamethasone was chronically given by intraperitoneal injection once a day for one week or was acutely washed into the brain slices. The neuronal spikes and synaptic transmission were recorded by whole-cell patching in amygdala neurons of brain slices. The chronic or acute administration of dexamethasone downregulates glutamate release as well as upregulates GABA release and GABAergic neuron spiking. The chronic administration of dexamethasone also enhances the responsiveness of GABA receptors. Conclusion: The upregulation of GABAergic neurons and the downregulation of glutamatergic neurons by glucocorticoid impair their balance in the amygdala, which leads to emotional disorders during stress.

研究背景：应激性生活可引发情绪障碍。慢性轻度应激被认为是抑郁症的主要病因，而急性重度应激则会诱发焦虑症。此类应激状态可能损伤下丘脑-垂体-肾上腺轴（hypothalamus-pituitary-adrenal axis），进而导致突触功能障碍。然而，应激激素如何扰乱亚细胞区室以及兴奋性与抑制性神经元之间的相互作用，目前仍尚不明确。本研究以与情绪状态密切相关的小鼠杏仁核为研究对象，针对这一科学问题展开了探究。方法与结果：本研究采用两种方式给予地塞米松（Dexamethasone）：一是通过腹腔注射每日给药一次，连续给药一周以构建慢性给药模型；二是将其急性灌流至脑片培养基中。采用全细胞膜片钳技术记录脑片杏仁核神经元的放电活动与突触传递过程。结果显示，无论是慢性还是急性给予地塞米松，均可下调谷氨酸释放量，同时上调γ-氨基丁酸（GABA）释放量以及γ-氨基丁酸能神经元（GABAergic neuron）的放电水平；慢性给予地塞米松还可增强γ-氨基丁酸受体（GABA receptor）的响应性。研究结论：糖皮质激素（glucocorticoid）对γ-氨基丁酸能神经元的上调作用与对谷氨酸能神经元的下调作用，破坏了杏仁核内两类神经元的平衡状态，进而在应激过程中引发情绪障碍。